PROJECTSUMMARY Biomedical research is becoming increasingly dependent on construction and simulation of computational models.Arguablythiswillbeevenmorethecasewiththedevelopmentofpersonalizedmedicine.However, thetechnicalaspectsofmodelingandsimulationareoverwhelmingtomanybiomedicalresearchers.Whatis neededisasoftwareapplicationcapableofprovidingtheappropriatenumericalalgorithms,butshieldedbya user interface that aides the biomedical researcher in conducting the required simulations. Modeling and simulation can be applied at the level of molecules, their networks, cells, tissues and whole organisms. Sometimesseveraloftheselevelshavetoberepresentedinordertoproperlypredictandunderstandhealth and disease. Thus models are becoming larger, multiscale, and require various different mathematical frameworks for simulation. We propose to address this need with continuing development of the COPASI software,whichisalreadywidelyusedinthebiomedicalresearchcommunity,addressingthecurrenttrends. ThisprojectwillalsoprovidesupporttothevibrantcommunityofCOPASIusers/biomedicalresearchers.We willaddressthiswiththefollowingSpecificAims: Aim1.Addnewnumericalsimulationandanalysismethodstofurthersupportbiomedicalresearch.Wewill develop and add new hybrid simulation algorithms to address models that require some of its parts to be simulatedindifferentframeworks.Wewilladdanewtasktoanalyzeparameteridentifiability,whichisvery usefulforfindingoutifthemodelanddataarematched,orimprovementsneedtobemadeinboth. Aim2.ImproveCOPASI?suserinterfaceandtheinterfaceswithothersoftware.Wewillimprovethegraphical user interface to allow it to efficiently manipulate very large models. We will create a new programming interfacesothatotherscaneasilyuseCOPASI?sfunctionsfromotherprograms. Aim3.Softwaremaintenanceandstandardscompliance.Wewillcontinuetomaintainthesoftware,correcting errorsandmakingimprovements,guidedbyfeedbackcollectedfromitsusers.Wewillcontinuetoimplement standardscompliancetoensurethesoftwareisinteroperablewithotherapplications. Aim 4. Support the modeling community. We will continue outreach program activities aimed helping biomedicalresearchersmakefulluseofthesoftware?scapabilities.Thisincludescontinuingtooffertutorials, courses,andworkshops?tocreatefurthertrainingvideosandtomaintainawebbaseddiscussiongroup.